The broad aim of this research is to study the mechanisms by which hormones regulate enzyme levels in mammalian tissues. I will concentrate on the enzyme P-enolpyruvate carboxykinase which plays a key role in hepatic gluconeogenesis. Immunochemical procedures for the study of enzyme turnover have been developed in our laboratory and preliminary data indicate that it will serve as an excellent model for investigating the mechanisms controlling the synthesis and degradation of enzymes. More specifically I propose to study: 1) The mechanisms of glucose and insulin deinduction of hepatic P-enolpyruvate carboxykinase. 2) Factors regulating the turnover of specific P-enolpyruvate carboxykinase mRNA. 3) The mechanisms by which glucocorticoids decrease the rate of P-enolpyruvate carboxykinase synthesis in rat liver. 4) The hormonal regulation of P-enolpyruvate carboxykinase activity at birth. 5) The mechanisms regulating the degradation of P-enolpyruvate carboxykinase in rat liver. 6) The regulation of P-enolpyruvate carboxykinase in rat kidney, with special emphasis on the mechanism of acid-base status on enzyme synthesis. BIBLIOGRAPHIC REFERENCES: Hanson, R.W., Reshef, L. and Ballard, F.J. The hormonal regulation of hepatic P-enolpyruvate and carboxykinase (GTP) during development. Fed. Proc., 34: 166, 1975. Gunn, J.M., Meyuhas, O., Reshef, L., Ballard, F.J. and Hanson, R.W. Glucocorticoids and the regulation of P-enolpyruvate carboxykinase (GTP) in the rat. Biochem. J., 150: 195-203, 1975.